JP2004077476A - Apparatus for injecting/mixing liquid droplets - Google Patents

Apparatus for injecting/mixing liquid droplets Download PDF

Info

Publication number
JP2004077476A
JP2004077476A JP2003285386A JP2003285386A JP2004077476A JP 2004077476 A JP2004077476 A JP 2004077476A JP 2003285386 A JP2003285386 A JP 2003285386A JP 2003285386 A JP2003285386 A JP 2003285386A JP 2004077476 A JP2004077476 A JP 2004077476A
Authority
JP
Japan
Prior art keywords
drop
electrode
injector
insulating layer
droplet
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
JP2003285386A
Other languages
Japanese (ja)
Inventor
Yves Fouillet
イブ、フイエ
Jean Luc Achard
ジャン‐リュック、アシャール
Olivier Fuchs
オリビエ、フューシュ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Original Assignee
Commissariat a lEnergie Atomique CEA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Commissariat a lEnergie Atomique CEA filed Critical Commissariat a lEnergie Atomique CEA
Publication of JP2004077476A publication Critical patent/JP2004077476A/en
Withdrawn legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0244—Drop counters; Drop formers using pins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/302—Micromixers the materials to be mixed flowing in the form of droplets
    • B01F33/3021—Micromixers the materials to be mixed flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/714—Feed mechanisms for feeding predetermined amounts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/71755—Feed mechanisms characterised by the means for feeding the components to the mixer using means for feeding components in a pulsating or intermittent manner
    • B01F35/717551—Feed mechanisms characterised by the means for feeding the components to the mixer using means for feeding components in a pulsating or intermittent manner using electrical pulses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/23—Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0812—Bands; Tapes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/02—Drop detachment mechanisms of single droplets from nozzles or pins
    • B01L2400/027—Drop detachment mechanisms of single droplets from nozzles or pins electrostatic forces between substrate and tip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/85—Investigating moving fluids or granular solids
    • G01N2021/8557—Special shaping of flow, e.g. using a by-pass line, jet flow, curtain flow
    • G01N2021/8564—Sample as drops
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1046—Levitated, suspended drops
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Electrostatic Spraying Apparatus (AREA)
  • Nozzles (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus for injecting/mixing liquid droplets for mixing a first droplet with a second droplet on an electrical insulating layer of an analyzing support. <P>SOLUTION: The apparatus mixes the second droplet 1b with the first droplet 1a placed on the electrical insulating layer 14 of the analyzing support 7 under the environment of viscous liquid, and mixes the resultant droplets. The apparatus includes at least one injector 8 for forming the second droplet 1b on the first droplet 1a. After the formation of the second droplet 1b, a voltage impulse is applied between a first electrode 17, which is placed under the electrical insulating layer 14 of the analyzing support 7 under the first droplet 1a, and a second electrode 18 which is placed in the vicinity of an outlet orifice 10 of the injector 8. The voltage impulse accelerates the coalescence between the two droplets 1a, 1b, and prevents the possibility of pollution of the injector 8 caused by the reagent of the first droplet 1a. <P>COPYRIGHT: (C)2004,JPO

Description

　本発明は、分析支持体の電気絶縁層に置かれた第１滴に、第２滴を混合するための手段を備え、液体小滴を噴射および混合するための装置に関する。 The present invention relates to an apparatus for jetting and mixing liquid droplets, comprising means for mixing a second drop with a first drop placed on an electrically insulating layer of an analysis support.

　生物学、化学または光学、および、特にチップラボまたはラボ・オン・ア・チップなどの数多くの分野において、多数のサンプルを準備し、処理し、それから分析することが必要とされる。これは、少量の液体を流れさせ、または操作しなければならないことを意味する。マイクロ流体工学は、例えば、少量の液体を、マイクロ機械加工されたチャネルに流れさせることを可能にする。他のアプローチは、例えば、２つの異なる試薬を混合するために、液体の小滴を操作し、合流させることに存する。また、この合流から生じる滴を、分析することが可能である。 In many fields, such as biology, chemistry or optics, and especially chip labs or labs on a chip, it is necessary to prepare, process and then analyze a large number of samples. This means that a small amount of liquid must be flowed or manipulated. Microfluidics, for example, allows a small amount of liquid to flow through a micromachined channel. Another approach consists in manipulating and combining liquid droplets, for example, to mix two different reagents. It is also possible to analyze the drops resulting from this merge.

　特に静電気力を用いて、液体の滴を操作する、数多くの方法が存在する。このため、M. G. Pollackらによる論文“Electrowetting-based actuation of liquid droplets for microfluidic applications”（Applied Physics Letters, vol 77, pp 1725-1726, 2000）では、エレクトロウェッティング現象に基づいた、小滴を移動させるための静電的方法が記述されており、この方法は、小滴の表面張力を電気的に制御し、小滴を１２０ボルトまでの電圧で動かすことを可能にする。小滴は、薄いテフロン（登録商標）タイプのフッ素化重合体の堆積により疎水性にされた、電気絶縁層で覆われた電極を含む２つの面の間に置かれる。小滴を、固定された毛細管により、２つの面の間に噴射することができる。 There are a number of ways to manipulate liquid drops, especially using electrostatic forces. For this reason, the paper “Electrowetting-based actuation of liquid droplets for microfluidic applications” by MG Pollack et al. (Applied Physics Letters, vol 77, pp 1725-1726, 2000) moves droplets based on the electrowetting phenomenon. An electrostatic method is described for this, which electrically controls the surface tension of the droplets and allows the droplets to be moved at voltages up to 120 volts. The droplet is placed between two faces comprising an electrode covered with an electrically insulating layer, rendered hydrophobic by the deposition of a thin Teflon type fluorinated polymer. A droplet can be ejected between two surfaces by a fixed capillary.

　A. Torkkeliらによる論文“Droplets manipulation on a superhydrophobic surface for micro-chemical analysis”（Transducers’01 Eurosensors XV, 10-14 June 2001）には、滴１を、ウエハ２の疎水性表面３に直接置いた、オープンシステムが記述されている（図１）。絶縁膜５で覆われた複数の並列電極４が、ウエハ２の上に配置され、静電気力を発生させ、１つの電極から他の電極へ、図２に矢印で示した方向で、水平に滴１を移動させる。滴１ａと滴１ｂは、それらの移送パスが交わる場所で混合され（図２）、滴１ｃを形成する。滴１ｃは、次に、滴１ｄと接触し、滴１ｅを形成する。滴１ｅは、２つの滴１ｆと１ｇに分離され、分析される。滴は、ウエハ２内に形成された穴６を通して汲み出され、表面３に置かれる（図３）。このため、オリフィス６において、生物学的汚染のリスクがある。 In the paper “Droplets manipulation on a superhydrophobic surface for micro-chemical analysis” by A. Torkkeli et al. (Transducers'01 Eurosensors XV, 10-14 June 2001), Drop 1 was placed directly on the hydrophobic surface 3 of wafer 2 An open system is described (FIG. 1). A plurality of parallel electrodes 4 covered with an insulating film 5 are disposed on the wafer 2 to generate electrostatic force and drop horizontally from one electrode to another in the direction indicated by the arrow in FIG. Move 1 Drops 1a and 1b are mixed where their transfer paths meet (FIG. 2) to form drop 1c. Drop 1c then contacts drop 1d to form drop 1e. Drop 1e is separated into two drops If and 1g and analyzed. The drops are pumped through holes 6 formed in the wafer 2 and placed on the surface 3 (FIG. 3). For this reason, there is a risk of biological contamination at the orifice 6.

　本発明の目的は、噴射手段の生物学的汚染を防ぐとともに、噴射され混合される滴の量を制御し、再現可能な噴射および混合プロセスの間、また、分析プロセスの間に、滴の蒸発を防止する、小滴を噴射および混合するための装置を達成することである。 The object of the present invention is to prevent biological contamination of the ejection means and to control the amount of droplets that are ejected and mixed so that the evaporation of the droplets during a reproducible ejection and mixing process and also during the analysis process. To achieve an apparatus for jetting and mixing droplets.

　本発明によれば、この目的は、混和性を持たない第１滴および第２滴の粘性液体を、分析支持体の電気絶縁層に堆積すること、および、装置は、第２滴を、出口オリフィスにおいて、第１滴の上に形成するように設計された、少なくとも１つの噴射器を備えること、装置は、第１滴の下において、分析支持体の電気絶縁層の下に配置された第１電極と、噴射器の出口オリフィスの近くに配置された第２電極との間に印加される電圧を、制御するための制御手段を備えること、によって達成される。 According to the present invention, the object is to deposit a first drop and a second drop of a non-miscible viscous liquid on the electrically insulating layer of the analytical support, and the device takes the second drop into the outlet. Providing at least one injector designed to form on the first drop at the orifice, the apparatus is arranged under the first drop and below the electrically insulating layer of the analysis support. This is accomplished by providing control means for controlling the voltage applied between one electrode and a second electrode located near the exit orifice of the injector.

　本発明の開発において、分析支持体の電気絶縁層は、第１電極を形成する導電帯を備える電気絶縁支持体上に配置される。 In the development of the present invention, the electrical insulating layer of the analytical support is placed on the electrical insulating support with a conductive band forming the first electrode.

　本発明の目的は、また、結果として生じる小滴の内容物を、混合することである。 The purpose of the present invention is also to mix the contents of the resulting droplets.

　この目的は、特に、制御手段は、第１電極および第２電極を、噴射器による第２滴の形成の間、同一の電位に設定するための手段と、第１電圧インパルスを、第１電極と第２電極との間で、第２滴の形成後に、約数ミリ秒から１秒の第１期間の間、印加するための手段とを備えることによって達成される。 In particular, the control means comprises means for setting the first electrode and the second electrode at the same potential during the formation of the second drop by the injector, and the first voltage impulse, And means for applying between the second electrode and the second electrode for a first period of about several milliseconds to 1 second after formation of the second drop.

　本発明の１つの特徴によれば、制御手段は、第２電圧インパルスを、第１電極と第２電極の間で、第１インパルス後の約数ミリ秒から数秒の第２期間の間、印加するための手段を備える。 According to one feature of the invention, the control means applies the second voltage impulse between the first electrode and the second electrode for a second period of about several milliseconds to a few seconds after the first impulse. Means for doing so.

　他の利点および特徴は、以下に述べる本発明の特定の実施形態の記述によって、より明確となり、これらは、非限定的な実施例としてのみ提供され、添付の図面により表現される。 Other advantages and features will become more apparent from the description of specific embodiments of the invention described below, which are provided as non-limiting examples only and are represented by the accompanying drawings.

　本発明は、数ナノリットルから数マイクロリットルの小滴を、分析支持体上にて合体させることに存する。滴のサイズが比較的小さいため、噴射および混合プロセスの間、また、分析プロセスの間において、小滴の蒸発を防ぐ必要がある。このためには、小滴の噴射および混合プロセスを、小滴が混和性を持たない粘性液体環境において行えばよい。例えば、粘性液体を油とする一方で、小滴を水溶液により形成することができる。 The present invention consists in combining droplets of several nanoliters to several microliters on an analysis support. Due to the relatively small size of the droplets, it is necessary to prevent droplet evaporation during the jetting and mixing process and also during the analysis process. To this end, the droplet ejection and mixing process may be performed in a viscous liquid environment where the droplets are not miscible. For example, droplets can be formed with an aqueous solution while the viscous liquid is oil.

　しかしながら、滴１ｂを滴１aに単に噴射して、滴１ｃを形成する場合、図４に表わすように、滴を噴射する際の生物学的汚染のリスクは最大になる。このケースでは、第１滴１ａは、分析支持体７に置かれている。噴射器８は、第２滴１ｂを、第１滴１ａの上に、出口オリフィス１０を通して形成し、第２滴１ｂを、第１滴１ａと合体させ、第３滴１ｃを形成させる。噴射器の出口オリフィス１０が第１滴１ａに近い場合、第１滴１ａと第２滴１ｂの合体現象の後に、第３滴１ｃが、噴射器８の出口オリフィス１０と接触したままになることがある。このため、出口オリフィス１０は、第１滴１ａの残留物１１を含みやすく、それによって汚染されやすくなる。これにより、噴射器が、他の第１滴１ａと混合するための、他の第２滴１ｂを形成する際に、他の滴を汚染しやすくなる。 However, if the drop 1b is simply jetted onto the drop 1a to form the drop 1c, the risk of biological contamination when jetting the drop is maximized, as shown in FIG. In this case, the first drop 1 a is placed on the analysis support 7. The injector 8 forms a second drop 1b on the first drop 1a through the exit orifice 10, and combines the second drop 1b with the first drop 1a to form a third drop 1c. When the outlet orifice 10 of the injector is close to the first drop 1a, the third drop 1c remains in contact with the outlet orifice 10 of the injector 8 after the coalescence of the first drop 1a and the second drop 1b. There is. For this reason, the exit orifice 10 is likely to contain the residue 11 of the first drop 1a, thereby being easily contaminated. Thereby, when forming the other 2nd droplet 1b for an injector to mix with the other 1st droplet 1a, it becomes easy to contaminate another droplet.

　E. Chervenivanova らによる、論文“On the deformation of two droplets in a quasisteady Stokes flow”（Int. J. Multiphase Flow, Vol 11, n°5, p721-738, 1985）によると、２つの滴１ａおよび１ｂが、粘性液体環境９において、互いに向かう動きは、結果として、２つの滴の間に、粘性液体環境９の排出流１２を生じさせる（図５）。排出流１２は、一般的に、機械的または重力的原因により、滴１ａおよび滴１ｂが互いに向かって動く速度と比べて遅すぎるので、結果として後者に歪みが生じる。その後、窪み１３が出現する。この作用は、直ちに、排出全体において、滴の合体に対抗する。排出時間が長いほど、液体環境９の粘性が上がる。排出時間は、従って、大きく変化し、１分以上継続することがあり、合体プロセスをほとんど再現不可能にする。 According to the paper “On the deformation of two droplets in a quasisteady Stokes flow” by E. Chervenivanova et al. (Int. J. Multiphase Flow, Vol 11, n ° 5, p721-738, 1985), two drops 1a and 1b However, movement toward each other in the viscous liquid environment 9 results in a discharge stream 12 of the viscous liquid environment 9 between the two drops (FIG. 5). The discharge stream 12 is generally too slow compared to the speed at which the drops 1a and 1b move towards each other due to mechanical or gravitational causes, resulting in distortion of the latter. Thereafter, the depression 13 appears. This action immediately counteracts the coalescence of drops throughout the discharge. The longer the discharge time, the higher the viscosity of the liquid environment 9. The drain time thus varies greatly and can last for more than 1 minute, making the coalescence process almost non-reproducible.

　既知の噴射器の使用では、上述の欠点を克服することができない。例えば、極小の小滴を静電気力によってノズルから噴射することができる、いわゆる“エレクトロスプレー”方法を用いた噴射器は、高い粘性を有する液体環境では適用することができない。 The use of known injectors cannot overcome the above-mentioned drawbacks. For example, an ejector using a so-called “electrospray” method, in which a very small droplet can be ejected from a nozzle by electrostatic force, cannot be applied in a highly viscous liquid environment.

　一方で、本発明による、液体小滴を噴射および混合するための装置では、特に次のことを可能にする。　
−２つの滴を、比較的粘性のある液体環境で合体させることにより、試薬混合物を得る。
−噴射器の出口オリフィスを、第１滴１ａを形成する試薬で汚染しない。　
−噴射器により噴射される第２滴の量を制御する。　
−再現可能な噴射および混合プロセスを達成する。 On the other hand, the device for jetting and mixing liquid droplets according to the invention makes it possible in particular to:
-Reagent mixture is obtained by combining the two drops in a relatively viscous liquid environment.
-The outlet orifice of the injector is not contaminated with the reagent forming the first drop 1a.
-Controlling the amount of the second drop ejected by the ejector.
Achieve a reproducible injection and mixing process.

　図６に表わす、第１実施形態によれば、噴射および混合装置は、第１滴１ａが置かれる電気絶縁層１４を有する分析支持体７を備える。噴射器８は、第２滴１ｂを、出口オリフィス１０を通して形成するよう設計されており、毛細管１５の第１端に結合され、この毛細管１５の第２端は、第２滴１ｂを構成する試薬を含む容積ポンプ１６に結合されている。噴射器８は、第２滴１ｂを第１滴１ａと合体させるよう、第１滴１ａの上に配置されている。 According to the first embodiment represented in FIG. 6, the jetting and mixing device comprises an analysis support 7 having an electrically insulating layer 14 on which the first drop 1a is placed. The injector 8 is designed to form a second drop 1b through the outlet orifice 10 and is coupled to the first end of the capillary 15 which is the reagent that constitutes the second drop 1b. Is coupled to a volumetric pump 16 including The injector 8 is disposed on the first drop 1a so as to unite the second drop 1b with the first drop 1a.

　噴射、混合および分析プロセスの間に、滴１ａおよび滴１ｂの蒸発を防ぐために、先に、粘性液体が、分析支持体７の電気絶縁層１４に堆積される。第１滴１ａおよび第２滴１ｂは、粘性液体中では不混和性である。滴は、例えば、水溶液であり、一方で、粘性液体は、油または有機液体である。第１滴１ａは、任意の適切な手段、例えば、毛細管または噴射器８のタイプの噴射器などにより、電気絶縁層１４に配置される。 During the spraying, mixing and analysis process, a viscous liquid is first deposited on the electrically insulating layer 14 of the analysis support 7 in order to prevent evaporation of the drops 1a and 1b. The first drop 1a and the second drop 1b are immiscible in the viscous liquid. The droplet is, for example, an aqueous solution, while the viscous liquid is an oil or an organic liquid. The first drop 1a is placed on the electrically insulating layer 14 by any suitable means, such as a capillary or an injector of the type of injector 8.

　滴の合体現象は、電圧発生器１９に接続される第１電極１７および第２電極１８により発生される、静電気力によって促進される。第１電極１７は、第１滴１ａの下に位置するように、分析支持体７の電気絶縁層１４の下に配置される。第２電極１８は、第２滴１ｂの近くになるように、噴射器の出口オリフィスの近くに配置される。図６において、第２電極１８は、噴射器８の壁の一部を囲む導体材料により形成されている。 Drop coalescence is promoted by electrostatic force generated by the first electrode 17 and the second electrode 18 connected to the voltage generator 19. The first electrode 17 is disposed under the electrically insulating layer 14 of the analysis support 7 so as to be located under the first drop 1a. The second electrode 18 is positioned near the exit orifice of the injector so as to be near the second drop 1b. In FIG. 6, the second electrode 18 is formed of a conductive material surrounding a part of the wall of the injector 8.

　容積ポンプにより、噴射器８の出口オリフィス１０における、第２滴１ｂの形成の制御が可能となり、２つの電極は、第２滴１ｂの形成の間、同一の電位に設定される。次に、第１電圧インパルスが、第１電極１７および第２電極１８の間に、例えば、約数ミリ秒から１秒のプリセット時間の間、印加される。電圧は、高周波の直流または交流とすることができ、約数十または数百ボルトである。 The volumetric pump allows control of the formation of the second drop 1b at the outlet orifice 10 of the injector 8, and the two electrodes are set to the same potential during the formation of the second drop 1b. Next, the first voltage impulse is applied between the first electrode 17 and the second electrode 18 for a preset time of, for example, about several milliseconds to 1 second. The voltage can be high frequency direct current or alternating current and is about tens or hundreds of volts.

　第２滴１ｂの形成後に発生する静電気力は、前者の量に影響を及ぼさない。静電気力は、第１滴１ａおよび第２滴１ｂに、相互引力を発生させ、その結果、２つの滴の即時の結合により、第２滴１ｂが第１滴１ａに移される（図７および図８）。 The electrostatic force generated after the formation of the second drop 1b does not affect the former amount. The electrostatic force generates a mutual attractive force on the first drop 1a and the second drop 1b, so that the second drop 1b is transferred to the first drop 1a by the immediate combination of the two drops (FIGS. 7 and FIG. 7). 8).

　図７は、粘性液体９内での、第１滴１ａおよび第２滴１ｂの混合プロセスにおける、時間に対する進行を表している。この場合、噴射器８の出口オリフィス１０は、第２滴は出口オリフィス１０で形成される際、略円形であることを考慮して、第１滴１ａおよび第２滴１ｂの間の距離ｄが、第２滴の平均直径以下となるように配置されている。このため、平均直径は、０．２５μｌの滴に対して、約１ミリメートルとなる。滴１ａおよび滴１ｂの噴射および混合プロセスは、異なる時間ａ〜ｈで表されており、時間ａとｇの間で、１つの時間から次の時間へ進むのに必要な時間の経過は、約１ミリ秒である。 FIG. 7 shows the progress of the mixing process of the first drop 1a and the second drop 1b in the viscous liquid 9 with respect to time. In this case, the exit orifice 10 of the injector 8 has a distance d between the first drop 1a and the second drop 1b, taking into account that the second drop is formed in the exit orifice 10 and is substantially circular. The second droplets are arranged so as to have an average diameter or less. This results in an average diameter of about 1 millimeter for a 0.25 μl drop. The droplet 1a and droplet 1b jetting and mixing processes are represented by different times ah, and the time lapse required to go from one time to the next between times a and g is about 1 millisecond.

　時間ａにて、第１滴と第２滴は、滴の平均直径以下の距離ｄをおいて離されている。第２滴１ｂの形成後に印加される静電気力によって、第１滴１ａおよび第２滴１ｂは歪められ、後者は、時間ｂで表わされるように、互いに引きつけ合う。２つの滴は、次の時間ｃにて、結合を促す円錐形となり、これは、図５で示した、合体現象に対抗する窪みが出現する場合と異なる。このように、２つの滴１ａおよび１ｂの引力が弾性を持ち、これらの作用形態により２つの滴１ａおよび１ｂの界面を歪ませ、窪みの存在を除去して、環境の排出を好適に加減する。第２滴１ｂの試薬が、次に、第１滴１ａの試薬に流れ込み、時間ｄにて、第２滴１ｂの試薬は、第１滴１ａの中心に浸透し、結果として、第１滴１ａの試薬の流れが、形成１ｃの新しい滴の周囲に生じる（時間ｄにて表わす）。 At time a, the first drop and the second drop are separated by a distance d that is equal to or less than the average diameter of the drops. The electrostatic force applied after the formation of the second drop 1b distorts the first drop 1a and the second drop 1b, and the latter attracts each other as represented by time b. At the next time c, the two drops have a conical shape that promotes bonding, which is different from the case shown in FIG. 5 where a dent against the coalescence phenomenon appears. In this way, the attractive force of the two drops 1a and 1b has elasticity, and by these modes of action, the interface between the two drops 1a and 1b is distorted, and the presence of the depression is removed, thereby suitably controlling the discharge of the environment. . The reagent of the second drop 1b then flows into the reagent of the first drop 1a, and at time d, the reagent of the second drop 1b penetrates into the center of the first drop 1a, resulting in the first drop 1a. A flow of reagent occurs around a new drop of formation 1c (represented by time d).

　新しい滴１ｃは、次に、第１滴の試薬が、噴射器８の出口オリフィス１０のレベルまで高まる前に、噴射器より離れる（時間ｅにて表わす）。従って、噴射器と第１滴１ａの試薬の間に接触がないため、起こり得る汚染を防止する。時間ｆにて、混合を促進する２つの試薬の巻き込みが、新しい滴１ｃ内で生じる。溶解後、新しい滴１ｃは、明確な円形をとり、自然な溶解現象は、時間ｇにて表わす２つの試薬の混合を確実にし、数秒後、時間ｈにて表わすように、混合物は均一となる。 The new drop 1c then leaves the injector (represented by time e) before the first drop of reagent rises to the level of the outlet orifice 10 of the injector 8. Accordingly, there is no contact between the injector and the reagent of the first drop 1a, thus preventing possible contamination. At time f, the entrainment of two reagents that promote mixing occurs in a new drop 1c. After dissolution, the new drop 1c takes a clear circular shape, and the natural dissolution phenomenon ensures the mixing of the two reagents represented by time g, and after a few seconds, the mixture becomes homogeneous as represented by time h. .

　第２電圧インパルスを、例えば、約数ミリ秒の第２プリセット期間の間、第１電極１７および第２電極１８の間に印加することで、混合プロセスを加速することが可能である。第２電圧インパルスは、時間ｇに対応する時間で印加することが好ましい。表面電荷が、新しい滴１ｃの界面に現れ、新しい滴１ｃの外側および内側に流れを作り出す。この流れは、新しい滴１ｃの内容物を、数ミリ秒から数秒で、均一にする。 It is possible to accelerate the mixing process by applying the second voltage impulse between the first electrode 17 and the second electrode 18 for a second preset period of, for example, about several milliseconds. The second voltage impulse is preferably applied at a time corresponding to the time g. A surface charge appears at the interface of the new drop 1c, creating a flow outside and inside the new drop 1c. This flow makes the contents of the new drop 1c uniform in a few milliseconds to a few seconds.

　図８は、粘性液体９内での、第１滴１ａおよび第１滴１ｂの混合プロセスにおける、時間に対する進行を表している。この場合、噴射器８の出口オリフィス１０は、距離ｄが第２滴１ｂの平均直径より大きくなるように配置されている。第２滴１ｂの形成の後に、時間ａにて、第１電圧インパルスが、第１電極および第２電極の間に印加され、結果として、時間ｂで表わすように、第１滴１ａおよび第２滴１ｂに歪みが生じる。第２滴１ｂは、次に、噴射器８から離れ（時間ｃ）、第１滴１ａと接触（時間ｄ）する前に、粘性液体９の中に自由落下する。 FIG. 8 shows the progress over time in the mixing process of the first drop 1a and the first drop 1b in the viscous liquid 9. In this case, the outlet orifice 10 of the injector 8 is arranged such that the distance d is larger than the average diameter of the second droplet 1b. After the formation of the second drop 1b, at time a, a first voltage impulse is applied between the first electrode and the second electrode, resulting in the first drop 1a and the second drop as represented by time b. Distortion occurs in the droplet 1b. The second drop 1b then leaves the injector 8 (time c) and falls freely into the viscous liquid 9 before contacting the first drop 1a (time d).

　図７で示す現象が、次に再現され、第２滴１ｂは第１滴１ａに浸透し（時間ｅ）、結果として、第１滴１ａの試薬の流れが、形成１ｃの新しい滴の周囲に生じる。第１滴１ａおよび第２滴１ｂの間の合体現象は、即時的かつ再現可能であり、時間ｄと時間ｅの間の時間経過は、わずか１０ミリ秒である。混合物は、数秒後には均一となる（時間ｆ）。 The phenomenon shown in FIG. 7 is then reproduced, with the second drop 1b penetrating into the first drop 1a (time e), so that the reagent flow of the first drop 1a is around the new drop of formation 1c. Arise. The coalescence phenomenon between the first drop 1a and the second drop 1b is immediate and reproducible, and the time course between time d and time e is only 10 milliseconds. The mixture becomes homogeneous after a few seconds (time f).

　上述のように、第２電圧インパルスを印加して、新しい滴１ｃ内の第１滴１ａおよび第２滴１ｂの試薬の混合現象を、対流により加速することができる。落下中の第２滴１ｂの速度は、約数ミリ／秒または数センチ／秒である。この場合、噴射器８と第１滴１ａの間には、接触はないので、第１滴１ａの試薬による噴射器の汚染のリスクはない。 As described above, by applying the second voltage impulse, the mixing phenomenon of the reagent of the first drop 1a and the second drop 1b in the new drop 1c can be accelerated by convection. The speed of the second drop 1b during the fall is about several millimeters / second or several centimeters / second. In this case, since there is no contact between the injector 8 and the first drop 1a, there is no risk of contamination of the injector by the reagent of the first drop 1a.

　本発明による噴射および混合装置は、図５の実施形態で述べたような、窪みの発生を防ぐという利点を提供する。この窪みは、粘性液体環境内での合体を遅らせ、さらに抑制する傾向がある。装置は、また、容積ポンプにより噴射される第２滴１ｂの量を、効率的に制御することを可能にし、この量は、印加される電圧、噴射器の形状、および２つの電極間の距離から独立している。混合および噴射プロセスは、また、再現可能であり、発生する流体力学現象自体も、再現可能である。 The injection and mixing device according to the present invention provides the advantage of preventing the formation of depressions as described in the embodiment of FIG. This depression tends to delay and further inhibit coalescence in a viscous liquid environment. The device also makes it possible to efficiently control the amount of the second drop 1b ejected by the volumetric pump, this amount being the applied voltage, the shape of the injector and the distance between the two electrodes Independent from. The mixing and jetting process is also reproducible, and the hydrodynamic phenomena that occur are themselves reproducible.

　装置は、噴射器の汚染のいかなるリスクも提示しない。例えば、医療診断分野などの、重要な混合および分析プロセスにおいては、噴射器８の出口オリフィス１０は、好ましくは、距離ｄが第２滴の平均直径より大きくなるような距離に配置され、一方、より重要でないプロセスにおいては、噴射器は、汚染のおそれなしに、第１滴により近く配置することができる。 The device does not present any risk of injector contamination. In important mixing and analysis processes, such as in the medical diagnostic field, for example, the outlet orifice 10 of the injector 8 is preferably positioned at a distance such that the distance d is greater than the average diameter of the second drop, In less important processes, the injector can be placed closer to the first drop without the risk of contamination.

　図９にて表わす、特定の実施形態によれば、分析支持体７は、セラミック、ガラスまたは重合体などの絶縁材により形成されており、第１電極１７を形成する導電帯を備えている。導電帯は、従来のマイクロテクノロジー技術により達成することができる。従って、例えば、第２電極１７は、金の層にフォトリソグラフィを行うことにより得ることができる。第１滴１ａが置かれる電気絶縁層１４は、樹脂、酸化物（ＳｉＯ２）、またはシリコン窒化物（Ｓｉ３Ｎ４）製のものが好ましい。 According to the particular embodiment represented in FIG. 9, the analysis support 7 is made of an insulating material such as ceramic, glass or polymer and has a conductive band forming the first electrode 17. The conduction band can be achieved by conventional microtechnology techniques. Therefore, for example, the second electrode 17 can be obtained by performing photolithography on the gold layer. The electrical insulating layer 14 on which the first droplet 1a is placed is preferably made of resin, oxide (SiO 2 ), or silicon nitride (Si 3 N 4 ).

　図９において、噴射器８は、容積ポンプ（図示せず）に結合され、その自由端に、毛細管を備えている。この毛細管は、ポリイミドで覆われた石英ガラス製のマイクロチューブが好ましい。噴射器８の出口オリフィス１０は、毛細管の一方の端により好適に形成され、他方の端は、容積ポンプに結合される。毛細管の直径は、約数ミクロンから数百ミクロンであり、第１滴および第２滴の量は、約数十ナノリットルから数百ナノリットルである。第１滴および第２滴は、選択された第１滴の噴射モードに応じて、異なる量とすることができる。 In Fig. 9, the injector 8 is coupled to a volumetric pump (not shown) and has a capillary tube at its free end. The capillary is preferably a quartz tube made of quartz glass covered with polyimide. The outlet orifice 10 of the injector 8 is preferably formed by one end of a capillary tube, the other end being coupled to a volumetric pump. The diameter of the capillary is about a few microns to a few hundred microns, and the volume of the first and second drops is about a few tens of nanoliters to a few hundred nanoliters. The first drop and the second drop can be of different amounts depending on the selected first drop ejection mode.

　第２電極１８は、噴射器８の壁の一部を好適に囲んでおり、特に、噴射器８の壁を覆う導電材により作ることができる。 The second electrode 18 suitably surrounds a part of the wall of the injector 8 and can be made of a conductive material that covers the wall of the injector 8 in particular.

　特定の実施形態においては、噴射器の一部を構成する毛細管は、第２電極を形成する金属管に取り付けられる。これは、実施が容易であり、数多くの生物学的および化学的分析プロセスに適合するという利点を提供する。第２電極は、実際に、第１滴および第２滴の試薬と接触することは、決してないので、電気分解現象に起因する気泡の発生を、防ぐことができる。 In certain embodiments, the capillary tube that forms part of the injector is attached to a metal tube that forms the second electrode. This provides the advantage of being easy to implement and compatible with numerous biological and chemical analysis processes. Since the second electrode is never in contact with the reagent of the first drop and the second drop, the generation of bubbles due to the electrolysis phenomenon can be prevented.

　図１０にて表わす、他の実施形態によると、第２電極１８は、噴射器８の出口オリフィス１０の近くに配置された金属針である。金属針は、例えば、金、アルミニウムまたはプラチナのスレッドである。金属針は、特定の生物学的適合性の問題を避けるために、パリレン（登録商標）、すなわちジパラキシリレンの二量体からなる重合体フィルム、または、テフロン（登録商標）タイプにより、覆うことができる。 According to another embodiment, represented in FIG. 10, the second electrode 18 is a metal needle disposed near the outlet orifice 10 of the injector 8. The metal needle is, for example, a gold, aluminum or platinum thread. Metal needles can be covered with a polymer film consisting of a dimer of Parylene (R), i.e. diparaxylylene, or a Teflon (R) type to avoid certain biocompatibility issues .

　図１１においては、毛細管により形成される噴射器８は、第２電極１８を形成する伝導マイクロチューブに固定されている。この伝導マイクロチューブは、例えば、アルミニウム製である。噴射器を形成する毛細管は、また、例えば、プラチナまたは金の金属層で覆うことができる。 In FIG. 11, the injector 8 formed by a capillary is fixed to a conductive microtube that forms the second electrode 18. This conductive microtube is made of, for example, aluminum. The capillaries that form the injector can also be covered with a metal layer of, for example, platinum or gold.

　図１２にて表わす、他の実施形態によれば、第１電極１７は、絶縁分析支持体７および絶縁層１４の間に配置される、少なくとも１つの導電層により形成される。 According to another embodiment, represented in FIG. 12, the first electrode 17 is formed by at least one conductive layer arranged between the insulating analysis support 7 and the insulating layer 14.

　噴射および混合装置は、また、複数の噴射器８を備え、異なる試薬を含む複数の第２滴を、単一の第１滴に、連続的に噴射する、または、単一の試薬を含むことが可能な複数の第２滴を、単一の試薬を含むことが可能な複数の第１滴に、同時に噴射することができる。このように、図１３において、７つの第１滴１ａの列を電気絶縁層１４に配置し、各第１滴１ａの上に配置された７つの噴射器８により、第２滴１ｂを、各第１滴１ａに同時に噴射することができる。 The spraying and mixing device also includes a plurality of injectors 8 and sequentially sprays a plurality of second drops containing different reagents into a single first drop or includes a single reagent. A plurality of second drops capable of being simultaneously sprayed onto a plurality of first drops capable of containing a single reagent. In this way, in FIG. 13, a row of seven first drops 1 a is arranged on the electrically insulating layer 14, and the seven drops 8 arranged on each first drop 1 a cause each second drop 1 b to be The first droplet 1a can be ejected simultaneously.

　各噴射器は、第２電極１８を備える。第１の変形においては、第１電極１７は、７つの第１滴１ａに対し、共通とすることができる。すなわち、第１電極１７は、第１滴１ａの列（図１３の左部分）の下に配置される連続ストリップ２０により形成される、導電帯により形成される。他の変形においては、各第１滴は、導電帯により形成される、第１電極１７上に配置される（図１３の右部分）。 Each injector includes a second electrode 18. In the first modification, the first electrode 17 can be common to the seven first drops 1a. That is, the first electrode 17 is formed by a conductive band formed by the continuous strip 20 disposed under the row of the first drops 1a (the left portion in FIG. 13). In another variant, each first drop is placed on the first electrode 17 formed by a conductive band (right part of FIG. 13).

　図１４にて表わす、他の特定の実施形態によれば、噴射および混合装置は、数多くの試薬の混合と、熱処理とを、並列に行うことを可能にする。分析支持体７は、電気絶縁層１４で覆われ、その上に第１滴１ａの列が、毛細管２２により置かれる。毛細管２２は、異なる試薬により構成される第１滴１ａを、電気絶縁層１４上に好適に置く。 According to another particular embodiment, represented in FIG. 14, the jet and mixing device allows a number of reagents to be mixed and heat-treated in parallel. The analysis support 7 is covered with an electrically insulating layer 14, on which a row of first drops 1 a is placed by means of capillaries 22. The capillary 22 suitably places the first drop 1 a composed of different reagents on the electrical insulating layer 14.

　電気絶縁層１４は、好ましくは、例えば、ポリカーボネート製で厚さが５０μｍのフレキシブルフィルムであり、フィルムは油９の層で覆われている。絶縁フィルムは、２つのコイル２１の回転により、移動する。分析支持体７は、好ましくは、プリセット位置２２に配置される温度制御手段を備え、滴１ａおよび滴１ｂがこれらの位置を通過する際に、異なる熱処理を施すことを可能にする。 The electrical insulating layer 14 is preferably a flexible film made of polycarbonate and having a thickness of 50 μm, for example, and the film is covered with a layer of oil 9. The insulating film moves as the two coils 21 rotate. The analysis support 7 is preferably provided with temperature control means arranged at the preset positions 22 so that different heat treatments can be applied as the drops 1a and 1b pass through these positions.

　噴射器８は、各第１滴１ａ上で、第１滴１ａの試薬とは異なる試薬を含む、第２滴１ｂを形成する。噴射器は、ロボット２３に固定される。ロボット２３は、噴射器８の移動を行い、これを、列の各第１滴１ａ上に、連続的に配置することを可能にする。滴１ｂの形成後、電圧インパルスを、第１電極および第２電極の間に印加し、新しい滴１ｃの結合現象と形成を促進する。図１３にて表わすように、第１電極１７は、第１滴１ａの列に対して共通とする、または、列の各第１滴１ａの下に配置することができる。 The injector 8 forms a second drop 1b containing a reagent different from the reagent of the first drop 1a on each first drop 1a. The injector is fixed to the robot 23. The robot 23 moves the injector 8 and makes it possible to place it continuously on each first drop 1a in the row. After formation of the droplet 1b, a voltage impulse is applied between the first electrode and the second electrode to promote the coupling phenomenon and formation of a new droplet 1c. As shown in FIG. 13, the first electrode 17 can be common to the row of first drops 1a, or can be placed under each first drop 1a in the row.

　次に、噴射器がすでに第２滴１ｂを噴射した第１滴１ａの異なる試薬で、噴射器を汚染することなしに、各第１滴１ａの各試薬と、第２滴１ｂの試薬を、混合することが可能となる。これは、各混合の後に、噴射器を洗わなくてよい、という利点を提供する。 Next, each of the reagents of each first drop 1a and the reagent of the second drop 1b without contaminating the injector with a different reagent of the first drop 1a that has already ejected the second drop 1b by the injector, It becomes possible to mix. This provides the advantage that the injector does not have to be washed after each mixing.

　他の試薬を、形成された新しい滴１ｃの列に混合するために、噴射器８と同一タイプの第２噴射器２４を、取り付けることができる。装置は、第２滴の噴射と形成の速度、絶縁フィルム１４の移動速度、および噴射器８と噴射器２４の移動速度に応じて、混合プロセスを、加速または減速可能にするという利点を提供する
　第１滴および第２滴を形成する各試薬は、例えば、ＤＮＡ、タンパク質、または生体組織などの、生物学的分子を含むことができる。 A second injector 24 of the same type as the injector 8 can be installed to mix other reagents into the row of new drops 1c formed. The apparatus provides the advantage of allowing the mixing process to be accelerated or decelerated depending on the speed of injection and formation of the second drop, the speed of movement of the insulating film 14 and the speed of movement of the injectors 8 and 24 Each reagent that forms the first drop and the second drop can include a biological molecule, such as, for example, DNA, protein, or biological tissue.

図１は、従来技術による、小滴を移動および混合するための装置を表わしている。FIG. 1 represents an apparatus for moving and mixing droplets according to the prior art. 図２は、従来技術による、小滴を移動および混合するための装置を表わしている。FIG. 2 represents an apparatus for moving and mixing droplets according to the prior art. 図３は、従来技術による、小滴を移動および混合するための装置を表わしている。FIG. 3 represents an apparatus for moving and mixing droplets according to the prior art. 図４は、噴射および混合装置の実施形態の模式的表現である。FIG. 4 is a schematic representation of an embodiment of an injection and mixing device. 図５は、従来技術による、粘性液体環境における２つの滴の接触を表現している。FIG. 5 represents the contact of two drops in a viscous liquid environment according to the prior art. 図６は、本発明による噴射および混合装置の第１実施形態の模式的表現である。FIG. 6 is a schematic representation of a first embodiment of an injection and mixing device according to the present invention. 図７は、図６による装置を使用した、第１および第２混合プロセスの時間に対する進行を、それぞれ表現している。FIG. 7 represents the progress over time of the first and second mixing processes, respectively, using the apparatus according to FIG. 図８は、図６による装置を使用した、第１および第２混合プロセスの時間に対する進行を、それぞれ表現している。FIG. 8 represents the progression over time of the first and second mixing processes, respectively, using the apparatus according to FIG. 図９は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 9 schematically represents various embodiments of the injection and mixing device according to the invention. 図１０は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 10 schematically represents various embodiments of the injection and mixing device according to the invention. 図１１は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 11 schematically represents various embodiments of the injection and mixing device according to the invention. 図１２は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 12 schematically represents various embodiments of the injection and mixing device according to the invention. 図１３は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 13 schematically represents various embodiments of the injection and mixing device according to the invention. 図１４は、本発明による噴射および混合装置のさまざまな実施形態を、模式的に表現している。FIG. 14 schematically represents various embodiments of the injection and mixing device according to the invention.

Claims (15)

　液体小滴を噴射および混合するための装置であって、
　分析支持体（７）の電気絶縁層（１４）に置かれた第１滴（１ａ）に、第２滴（１ｂ）を混合するための手段を備え、
　混和性を持たない前記第１滴（１ａ）および前記第２滴（１ｂ）の粘性液体を、前記分析支持体（７）の前記電気絶縁層（１４）上に堆積させ、
　前記装置は、前記第２滴（１ｂ）を、出口オリフィス（１０）において、前記第１滴（１ａ）上に形成するよう設計された、少なくとも１つの噴射器（８）を備え、
　前記装置は、前記第１滴（１ａ）の下において、前記分析支持体（７）の前記電気絶縁層（１４）の下に配置された第１電極（１７）と、前記噴射器（８）の前記出口オリフィス（１０）の近くに配置された第２電極（１８）との間に印加される電圧を、制御するための制御手段を備える、
　ことを特徴とする装置。 An apparatus for jetting and mixing liquid droplets,
Means for mixing the second drop (1b) with the first drop (1a) placed on the electrically insulating layer (14) of the analytical support (7);
Depositing the immiscible liquids of the first drop (1a) and the second drop (1b) on the electrically insulating layer (14) of the analytical support (7);
The apparatus comprises at least one injector (8) designed to form the second drop (1b) at the outlet orifice (10) on the first drop (1a);
The apparatus includes a first electrode (17) disposed under the first insulating layer (14) of the analytical support (7) under the first drop (1a), and the injector (8). Control means for controlling the voltage applied to the second electrode (18) disposed near the outlet orifice (10) of
A device characterized by that. 　前記第２電極（１８）は、金属針であることを特徴とする請求項１に記載の装置。 The apparatus according to claim 1, wherein the second electrode (18) is a metal needle. 　前記第２電極（１８）は、前記噴射器の壁の一部を囲んでいることを特徴とする請求項１に記載の装置。 The apparatus of claim 1, wherein the second electrode (18) surrounds a portion of the wall of the injector. 　前記噴射器（８）は、前記第２電極（１８）を形成する導電材によって、覆われていることを特徴とする請求項３に記載の装置。 The device according to claim 3, characterized in that the injector (8) is covered by a conductive material forming the second electrode (18). 　前記噴射器（８）は、その自由端において、容積ポンプ（１６）に結合された毛細管を備えることを特徴とする請求項１乃至４のいずれかに記載の装置。 Device according to any of the preceding claims, characterized in that the injector (8) comprises a capillary tube at its free end coupled to a volumetric pump (16). 　前記毛細管は、ポリイミドで覆われた石英ガラス製のマイクロチューブであることを特徴とする請求項５に記載の装置。 6. The apparatus according to claim 5, wherein the capillary is a quartz tube made of quartz glass covered with polyimide. 　前記分析支持体（７）の前記電気絶縁層（１４）は、第１電極（１７）を形成する導電帯を備える電気絶縁支持体に配置されていることを特徴とする請求項１乃至６に記載の装置。 7. The electrical insulation layer (14) of the analysis support (7) is arranged on an electrical insulation support comprising a conductive band forming a first electrode (17). The device described. 　前記帯は、前記絶縁層（１４）と前記電気絶縁支持体（７）との間に配置されている、少なくとも１つの導電層により形成されていることを特徴とする請求項７に記載の装置。 8. A device according to claim 7, characterized in that the strip is formed by at least one conductive layer arranged between the insulating layer (14) and the electrically insulating support (7). . 　前記帯は、第１滴（１ａ）の列の下に配置されている、連続ストリップ（２０）により形成されていることを特徴とする請求項７に記載の装置。 Device according to claim 7, characterized in that the strip is formed by a continuous strip (20), which is arranged below the row of first drops (1a). 　前記分析支持体（７）の前記電気絶縁層（１４）は、可動性であることを特徴とする請求項１乃至９のいずれかに記載の装置。 10. The device according to claim 1, wherein the electrical insulating layer (14) of the analytical support (7) is mobile. 　前記装置は、第１滴（１ａ）の列の上に、第２滴（１ｂ）を、同時に形成するために配置された、複数の噴射器（８）を備えることを特徴とする請求項１乃至１０のいずれかに記載の装置。 The apparatus comprises a plurality of injectors (8) arranged to simultaneously form a second drop (1b) on a row of first drops (1a). The apparatus in any one of thru | or 10. 　前記装置は、第２滴（１ｂ）を、連続的に形成するために配置された、複数の噴射器（８）を備えることを特徴とする請求項１乃至１０のいずれかに記載の装置。 Device according to any of the preceding claims, characterized in that the device comprises a plurality of injectors (8) arranged to continuously form the second drop (1b). 　前記制御手段は、
　前記第１電極（１７）および前記第２電極（１８）を、前記噴射器（８）による前記第２滴（１ｂ）の形成の間、同一の電位に設定するための手段と、
　前記第２滴（１ｂ）の形成後に、第１電圧インパルスを、前記第１電極（１７）と前記第２電極（１８）の間に、約数ミリ秒から１秒の第１期間の間、印加するための手段とを備える、ことを特徴とする請求項１乃至１２のいずれかに記載の装置。 The control means includes
Means for setting the first electrode (17) and the second electrode (18) to the same potential during the formation of the second drop (1b) by the injector (8);
After the formation of the second drop (1b), a first voltage impulse is applied between the first electrode (17) and the second electrode (18) for a first period of about several milliseconds to 1 second, 13. A device according to any preceding claim, comprising means for applying. 　前記制御手段は、第２電圧インパルスを、前記第１電極（１７）と前記第２電極（１８）の間に、前記第１インパルス後、約数ミリ秒から数秒の第２期間の間、印加するための手段を備えることを特徴とする請求項１３に記載の装置。 The control means applies a second voltage impulse between the first electrode (17) and the second electrode (18) for a second period of about several milliseconds to several seconds after the first impulse. The apparatus of claim 13, comprising means for: 　前記噴射器（８）の前記出口オリフィス（１０）は、前記第１滴（１ａ）と前記第２滴（１ｂ）の間の距離（ｄ）が、前記第２滴（１ｂ）の平均直径以下になるように配置されていることを特徴とする請求項１乃至１４のいずれかに記載の装置。 The outlet orifice (10) of the injector (8) has a distance (d) between the first drop (1a) and the second drop (1b) equal to or less than the average diameter of the second drop (1b). The device according to claim 1, wherein the device is arranged to be.
JP2003285386A 2002-08-01 2003-08-01 Apparatus for injecting/mixing liquid droplets Withdrawn JP2004077476A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR0209822A FR2843048B1 (en) 2002-08-01 2002-08-01 DEVICE FOR INJECTING AND MIXING LIQUID MICRO-DROPS.

Publications (1)

Publication Number Publication Date
JP2004077476A true JP2004077476A (en) 2004-03-11

Family

ID=30011623

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2003285386A Withdrawn JP2004077476A (en) 2002-08-01 2003-08-01 Apparatus for injecting/mixing liquid droplets

Country Status (6)

Country Link
US (1) US7211223B2 (en)
EP (1) EP1386657B8 (en)
JP (1) JP2004077476A (en)
AT (1) ATE314887T1 (en)
DE (1) DE60303107T2 (en)
FR (1) FR2843048B1 (en)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006201083A (en) * 2005-01-21 2006-08-03 Hitachi High-Technologies Corp Chemical analyzer and analytical device
JP2006521915A (en) * 2003-04-07 2006-09-28 エアストリーム テクノロジー リミティッド Spray electrode
JP2008515611A (en) * 2004-09-03 2008-05-15 ボストン サイエンティフィック リミティド Method of coating medical device using electrical infiltration method, system for using the method, and device manufactured by the method
JP2010510777A (en) * 2006-11-24 2010-04-08 エージェンシー フォー サイエンス，テクノロジー アンド リサーチ Apparatus for processing samples in droplets and methods of using the same
CN102018595A (en) * 2010-12-23 2011-04-20 中国人民解放军第二军医大学 Targeting inner ear droplet drug dispenser and use method thereof
US8261598B2 (en) 2006-03-09 2012-09-11 Agency For Science, Technology And Research Apparatus for performing a reaction in a droplet and method of using the same
US8784752B2 (en) 2009-04-17 2014-07-22 Curiox Biosystems Pte Ltd Use of chemically patterned substrate for liquid handling, chemical and biological reactions
JP5825618B1 (en) * 2015-02-06 2015-12-02 秋田県 Electrode for electric field stirring and electric field stirring method using the same
CN105939779A (en) * 2013-09-18 2016-09-14 加州理工学院 System and method for movement and timing control
US9557318B2 (en) 2013-07-09 2017-01-31 Curiox Biosystems Pte Ltd. Array plates for washing samples
US9874501B2 (en) 2006-11-24 2018-01-23 Curiox Biosystems Pte Ltd. Use of chemically patterned substrate for liquid handling, chemical and biological reactions
US9878328B2 (en) 2010-07-23 2018-01-30 Curiox Biosystems Pte Ltd. Apparatus and method for multiple reactions in small volumes
US9950323B2 (en) 2012-02-05 2018-04-24 Curiox Biosystems Pte Ltd. Array plates and methods for making and using same
US10545139B2 (en) 2015-06-16 2020-01-28 Curiox Biosystems Pte Ltd. Methods and devices for performing biological assays using magnetic components
US10725020B2 (en) 2007-11-14 2020-07-28 Curiox Biosystems Pte Ltd. High throughput miniaturized assay system and methods
US11692162B2 (en) 2017-04-05 2023-07-04 Curiox Biosystems Pte Ltd. Methods, devices, and apparatus for washing samples on array plates

Families Citing this family (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7470547B2 (en) * 2003-07-31 2008-12-30 Biodot, Inc. Methods and systems for dispensing sub-microfluidic drops
US6911132B2 (en) 2002-09-24 2005-06-28 Duke University Apparatus for manipulating droplets by electrowetting-based techniques
US7329545B2 (en) 2002-09-24 2008-02-12 Duke University Methods for sampling a liquid flow
ES2920892T3 (en) 2003-06-12 2022-08-11 Accupath Diagnostic Laboratories Inc Method for forming cell arrays
US20050084981A1 (en) * 2003-10-16 2005-04-21 Magdalena Ostrowski Method of depositing a bioactive material on a substrate
KR100552705B1 (en) * 2004-01-07 2006-02-20 삼성전자주식회사 Device for printing biomolecule using electrohydrodynamic effect on substrate and printing method thereof
EP1765501A1 (en) * 2004-05-28 2007-03-28 Board of Regents, The University of Texas System Programmable fluidic processors
DE602005024418D1 (en) 2004-08-26 2010-12-09 Life Technologies Corp ELECTROCONDUCTING DISPENSERS AND METHODS THEREFOR
WO2006081558A2 (en) 2005-01-28 2006-08-03 Duke University Apparatuses and methods for manipulating droplets on a printed circuit board
US7454988B2 (en) * 2005-02-10 2008-11-25 Applera Corporation Method for fluid sampling using electrically controlled droplets
US20060210443A1 (en) * 2005-03-14 2006-09-21 Stearns Richard G Avoidance of bouncing and splashing in droplet-based fluid transport
JP2008539759A (en) * 2005-05-11 2008-11-20 ナノリティックス・インコーポレイテッド Method and apparatus for performing biochemical or chemical reactions at multiple temperatures
KR100624467B1 (en) * 2005-05-13 2006-09-15 삼성전자주식회사 Device for printing biomolecule using electrohydrodynamic effect on substrate
FR2887305B1 (en) 2005-06-17 2011-05-27 Commissariat Energie Atomique DEVICE FOR PUMPING BY ELECTROWETTING AND APPLICATION TO MEASUREMENTS OF ELECTRIC ACTIVITY
KR100668343B1 (en) * 2005-08-12 2007-01-12 삼성전자주식회사 Device for printing bio-drop or ink using electric charge concentration effect on a substrate or a paper
US7556776B2 (en) * 2005-09-08 2009-07-07 President And Fellows Of Harvard College Microfluidic manipulation of fluids and reactions
US20070059213A1 (en) * 2005-09-15 2007-03-15 Lucent Technologies Inc. Heat-induced transitions on a structured surface
US8721161B2 (en) * 2005-09-15 2014-05-13 Alcatel Lucent Fluid oscillations on structured surfaces
US8734003B2 (en) * 2005-09-15 2014-05-27 Alcatel Lucent Micro-chemical mixing
KR101217550B1 (en) * 2006-01-26 2013-01-02 삼성전자주식회사 Device for controlling particle distribution in an evaporating droplet using radial electroosmotic flow
US8637317B2 (en) * 2006-04-18 2014-01-28 Advanced Liquid Logic, Inc. Method of washing beads
US20140193807A1 (en) 2006-04-18 2014-07-10 Advanced Liquid Logic, Inc. Bead manipulation techniques
US8492168B2 (en) * 2006-04-18 2013-07-23 Advanced Liquid Logic Inc. Droplet-based affinity assays
US9476856B2 (en) 2006-04-13 2016-10-25 Advanced Liquid Logic, Inc. Droplet-based affinity assays
US8613889B2 (en) * 2006-04-13 2013-12-24 Advanced Liquid Logic, Inc. Droplet-based washing
US7815871B2 (en) * 2006-04-18 2010-10-19 Advanced Liquid Logic, Inc. Droplet microactuator system
US7763471B2 (en) * 2006-04-18 2010-07-27 Advanced Liquid Logic, Inc. Method of electrowetting droplet operations for protein crystallization
US8658111B2 (en) 2006-04-18 2014-02-25 Advanced Liquid Logic, Inc. Droplet actuators, modified fluids and methods
US7816121B2 (en) * 2006-04-18 2010-10-19 Advanced Liquid Logic, Inc. Droplet actuation system and method
US7901947B2 (en) 2006-04-18 2011-03-08 Advanced Liquid Logic, Inc. Droplet-based particle sorting
US8809068B2 (en) 2006-04-18 2014-08-19 Advanced Liquid Logic, Inc. Manipulation of beads in droplets and methods for manipulating droplets
US8470606B2 (en) * 2006-04-18 2013-06-25 Duke University Manipulation of beads in droplets and methods for splitting droplets
WO2007123908A2 (en) 2006-04-18 2007-11-01 Advanced Liquid Logic, Inc. Droplet-based multiwell operations
US8716015B2 (en) 2006-04-18 2014-05-06 Advanced Liquid Logic, Inc. Manipulation of cells on a droplet actuator
US7439014B2 (en) * 2006-04-18 2008-10-21 Advanced Liquid Logic, Inc. Droplet-based surface modification and washing
US10078078B2 (en) 2006-04-18 2018-09-18 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
US8980198B2 (en) 2006-04-18 2015-03-17 Advanced Liquid Logic, Inc. Filler fluids for droplet operations
US8637324B2 (en) 2006-04-18 2014-01-28 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
US7851184B2 (en) * 2006-04-18 2010-12-14 Advanced Liquid Logic, Inc. Droplet-based nucleic acid amplification method and apparatus
WO2007124346A2 (en) * 2006-04-19 2007-11-01 Archivex Llc Micro-drop detection and detachment
US8041463B2 (en) * 2006-05-09 2011-10-18 Advanced Liquid Logic, Inc. Modular droplet actuator drive
US7822510B2 (en) * 2006-05-09 2010-10-26 Advanced Liquid Logic, Inc. Systems, methods, and products for graphically illustrating and controlling a droplet actuator
US7939021B2 (en) * 2007-05-09 2011-05-10 Advanced Liquid Logic, Inc. Droplet actuator analyzer with cartridge
US9675972B2 (en) 2006-05-09 2017-06-13 Advanced Liquid Logic, Inc. Method of concentrating beads in a droplet
WO2008089449A2 (en) 2007-01-19 2008-07-24 Biodot, Inc. Systems and methods for high speed array printing and hybridization
US8685344B2 (en) * 2007-01-22 2014-04-01 Advanced Liquid Logic, Inc. Surface assisted fluid loading and droplet dispensing
KR101431778B1 (en) 2007-02-09 2014-08-20 어드밴스드 리퀴드 로직, 아이엔씨. Droplet actuator devices and methods employing magnetic beads
WO2008101194A2 (en) 2007-02-15 2008-08-21 Advanced Liquid Logic, Inc. Capacitance detection in a droplet actuator
EP2126038B1 (en) 2007-03-22 2015-01-07 Advanced Liquid Logic, Inc. Enzymatic assays for a droplet actuator
US8202686B2 (en) * 2007-03-22 2012-06-19 Advanced Liquid Logic, Inc. Enzyme assays for a droplet actuator
AU2008237017B2 (en) * 2007-04-10 2013-10-24 Advanced Liquid Logic, Inc. Droplet dispensing device and methods
GB0707201D0 (en) * 2007-04-13 2007-05-23 Liquavista Bv Dispensing method and device for dispensing
DE102007018056A1 (en) * 2007-04-17 2008-10-23 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method and device for drop manipulation
WO2009002920A1 (en) 2007-06-22 2008-12-31 Advanced Liquid Logic, Inc. Droplet-based nucleic acid amplification in a temperature gradient
WO2009021233A2 (en) 2007-08-09 2009-02-12 Advanced Liquid Logic, Inc. Pcb droplet actuator fabrication
WO2009032863A2 (en) 2007-09-04 2009-03-12 Advanced Liquid Logic, Inc. Droplet actuator with improved top substrate
US20100236928A1 (en) * 2007-10-17 2010-09-23 Advanced Liquid Logic, Inc. Multiplexed Detection Schemes for a Droplet Actuator
US20100236929A1 (en) * 2007-10-18 2010-09-23 Advanced Liquid Logic, Inc. Droplet Actuators, Systems and Methods
CN103707643B (en) * 2007-12-23 2016-06-01 先进液体逻辑公司 The method of droplet actuator configuration and guiding droplet manipulation
FR2930457B1 (en) * 2008-04-24 2010-06-25 Commissariat Energie Atomique PROCESS FOR MANUFACTURING RECONFIGURABLE MICROCHANNELS
US9664619B2 (en) 2008-04-28 2017-05-30 President And Fellows Of Harvard College Microfluidic device for storage and well-defined arrangement of droplets
US8852952B2 (en) 2008-05-03 2014-10-07 Advanced Liquid Logic, Inc. Method of loading a droplet actuator
EP2286228B1 (en) * 2008-05-16 2019-04-03 Advanced Liquid Logic, Inc. Droplet actuator devices and methods for manipulating beads
US8286561B2 (en) 2008-06-27 2012-10-16 Ssw Holding Company, Inc. Spill containing refrigerator shelf assembly
US11786036B2 (en) 2008-06-27 2023-10-17 Ssw Advanced Technologies, Llc Spill containing refrigerator shelf assembly
WO2010042668A1 (en) 2008-10-07 2010-04-15 Ross Technology Corporation Spill resistant surfaces having hydrophobic and oleophobic borders
US8877512B2 (en) * 2009-01-23 2014-11-04 Advanced Liquid Logic, Inc. Bubble formation techniques using physical or chemical features to retain a gas bubble within a droplet actuator
US8926065B2 (en) 2009-08-14 2015-01-06 Advanced Liquid Logic, Inc. Droplet actuator devices and methods
US8846414B2 (en) 2009-09-29 2014-09-30 Advanced Liquid Logic, Inc. Detection of cardiac markers on a droplet actuator
US9074778B2 (en) 2009-11-04 2015-07-07 Ssw Holding Company, Inc. Cooking appliance surfaces having spill containment pattern
WO2011057197A2 (en) 2009-11-06 2011-05-12 Advanced Liquid Logic, Inc. Integrated droplet actuator for gel electrophoresis and molecular analysis
EP2516669B1 (en) 2009-12-21 2016-10-12 Advanced Liquid Logic, Inc. Enzyme assays on a droplet actuator
BR112012023312A2 (en) 2010-03-15 2019-09-24 Ross Tech Corporation plunger and hydrophobic surface production methods
EP2553473A4 (en) 2010-03-30 2016-08-10 Advanced Liquid Logic Inc Droplet operations platform
EP2588322B1 (en) 2010-06-30 2015-06-17 Advanced Liquid Logic, Inc. Droplet actuator assemblies and methods of making same
EP2665557B1 (en) 2011-01-21 2020-01-01 Biodot, Inc. Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube
JP2014512417A (en) 2011-02-21 2014-05-22 ロス テクノロジー コーポレーション． Superhydrophobic and oleophobic coatings containing low VOC binder systems
CA2833897C (en) 2011-05-09 2020-05-19 Advanced Liquid Logic, Inc. Microfluidic feedback using impedance detection
AU2012253595B2 (en) 2011-05-10 2016-10-20 Advanced Liquid Logic, Inc. Enzyme concentration and assays
US8901043B2 (en) 2011-07-06 2014-12-02 Advanced Liquid Logic, Inc. Systems for and methods of hybrid pyrosequencing
CN103733059B (en) 2011-07-06 2016-04-06 先进流体逻辑公司 Reagent on droplet actuator stores
US9513253B2 (en) 2011-07-11 2016-12-06 Advanced Liquid Logic, Inc. Droplet actuators and techniques for droplet-based enzymatic assays
US9446404B2 (en) 2011-07-25 2016-09-20 Advanced Liquid Logic, Inc. Droplet actuator apparatus and system
CN102430436A (en) * 2011-08-30 2012-05-02 复旦大学 Single-face controlled multi-electrode cluster digital micro-fluid chip
DE102011085428A1 (en) 2011-10-28 2013-05-02 Schott Ag shelf
WO2013078216A1 (en) 2011-11-21 2013-05-30 Advanced Liquid Logic Inc Glucose-6-phosphate dehydrogenase assays
EP2791255B1 (en) 2011-12-15 2017-11-01 Ross Technology Corporation Composition and coating for superhydrophobic performance
US9223317B2 (en) 2012-06-14 2015-12-29 Advanced Liquid Logic, Inc. Droplet actuators that include molecular barrier coatings
BR112014032676A2 (en) 2012-06-25 2017-06-27 Ross Tech Corporation elastomeric coatings that have hydrophobic and / or oleophobic properties
IN2015DN00359A (en) 2012-06-27 2015-06-12 Advanced Liquid Logic Inc
US9863913B2 (en) 2012-10-15 2018-01-09 Advanced Liquid Logic, Inc. Digital microfluidics cartridge and system for operating a flow cell
US11181448B2 (en) 2012-11-06 2021-11-23 Biodot, Inc. Controlled printing of a cell sample for karyotyping
CN115753300A (en) * 2015-04-20 2023-03-07 文塔纳医疗系统公司 Ink jet deposition of reagents for histological samples
WO2018073283A1 (en) 2016-10-19 2018-04-26 F. Hoffmann-La Roche Ag Systems and methods for staining of biological samples
CN113842963A (en) * 2021-10-29 2021-12-28 佛山奥素博新科技有限公司 Micro-droplet generation system and generation method
CN114383545B (en) * 2022-01-12 2022-09-27 四川文理学院 Device for measuring parallelism of micro electrode plate group

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4659677A (en) * 1983-05-26 1987-04-21 Eastman Kodak Company Method providing liquid mixing outside containers
JP3175132B2 (en) 1992-11-27 2001-06-11 住友電気工業株式会社 Optical transmitter
US5486337A (en) * 1994-02-18 1996-01-23 General Atomics Device for electrostatic manipulation of droplets
JP4433100B2 (en) * 1997-06-20 2010-03-17 ニューヨーク ユニヴァーシティ Electrostatic spraying of substance solutions in mass production of chips and libraries
US6149787A (en) * 1998-10-14 2000-11-21 Caliper Technologies Corp. External material accession systems and methods
JP2000152026A (en) 1998-11-10 2000-05-30 Matsushita Electric Ind Co Ltd Optical signal transmitter
US6977145B2 (en) * 1999-07-28 2005-12-20 Serono Genetics Institute S.A. Method for carrying out a biochemical protocol in continuous flow in a microreactor
EP1099484B1 (en) * 1999-11-11 2006-06-07 The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin A dispensing method and assembly for liquid droplets
JP2004500578A (en) * 2000-03-28 2004-01-08 カリパー・テクノロジーズ・コープ． Method for reducing fluid carryover in microfluidic devices
US6918309B2 (en) * 2001-01-17 2005-07-19 Irm Llc Sample deposition method and system
AU2002362446A1 (en) * 2001-10-03 2003-04-14 Kin Chiu Ng Apparatus and method for fabricating high density microarrays and applications thereof
US20030085952A1 (en) * 2001-11-05 2003-05-08 Williams Roger O Apparatus and method for controlling the free surface of liquid in a well plate

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006521915A (en) * 2003-04-07 2006-09-28 エアストリーム テクノロジー リミティッド Spray electrode
JP2008515611A (en) * 2004-09-03 2008-05-15 ボストン サイエンティフィック リミティド Method of coating medical device using electrical infiltration method, system for using the method, and device manufactured by the method
JP2006201083A (en) * 2005-01-21 2006-08-03 Hitachi High-Technologies Corp Chemical analyzer and analytical device
US8261598B2 (en) 2006-03-09 2012-09-11 Agency For Science, Technology And Research Apparatus for performing a reaction in a droplet and method of using the same
US8691147B2 (en) 2006-11-24 2014-04-08 Agency For Science, Technology And Research Apparatus for processing a sample in a liquid droplet and method of using the same
JP2010510777A (en) * 2006-11-24 2010-04-08 エージェンシー フォー サイエンス，テクノロジー アンド リサーチ Apparatus for processing samples in droplets and methods of using the same
US9581527B2 (en) 2006-11-24 2017-02-28 Agency For Science, Technology And Research Apparatus for processing a sample in a liquid droplet and method of using the same
US9874501B2 (en) 2006-11-24 2018-01-23 Curiox Biosystems Pte Ltd. Use of chemically patterned substrate for liquid handling, chemical and biological reactions
US10725020B2 (en) 2007-11-14 2020-07-28 Curiox Biosystems Pte Ltd. High throughput miniaturized assay system and methods
US8784752B2 (en) 2009-04-17 2014-07-22 Curiox Biosystems Pte Ltd Use of chemically patterned substrate for liquid handling, chemical and biological reactions
US10632468B2 (en) 2010-07-23 2020-04-28 Curiox Biosystems Pte Ltd. Apparatus and method for multiple reactions in small volumes
US9878328B2 (en) 2010-07-23 2018-01-30 Curiox Biosystems Pte Ltd. Apparatus and method for multiple reactions in small volumes
CN102018595A (en) * 2010-12-23 2011-04-20 中国人民解放军第二军医大学 Targeting inner ear droplet drug dispenser and use method thereof
US10792661B2 (en) 2012-02-05 2020-10-06 Curiox Biosystems Pte Ltd. Array plates and methods for making and using same
US9950323B2 (en) 2012-02-05 2018-04-24 Curiox Biosystems Pte Ltd. Array plates and methods for making and using same
US9557318B2 (en) 2013-07-09 2017-01-31 Curiox Biosystems Pte Ltd. Array plates for washing samples
US10207269B2 (en) 2013-09-18 2019-02-19 California Institute Of Technology System and method for movement and timing control
CN105939779A (en) * 2013-09-18 2016-09-14 加州理工学院 System and method for movement and timing control
JP5825618B1 (en) * 2015-02-06 2015-12-02 秋田県 Electrode for electric field stirring and electric field stirring method using the same
US10545139B2 (en) 2015-06-16 2020-01-28 Curiox Biosystems Pte Ltd. Methods and devices for performing biological assays using magnetic components
US11692162B2 (en) 2017-04-05 2023-07-04 Curiox Biosystems Pte Ltd. Methods, devices, and apparatus for washing samples on array plates

Also Published As

Publication number Publication date
DE60303107D1 (en) 2006-03-30
US20040136876A1 (en) 2004-07-15
EP1386657A1 (en) 2004-02-04
DE60303107T2 (en) 2006-08-31
EP1386657B8 (en) 2006-05-10
ATE314887T1 (en) 2006-02-15
FR2843048A1 (en) 2004-02-06
FR2843048B1 (en) 2004-09-24
US7211223B2 (en) 2007-05-01
EP1386657B1 (en) 2006-01-04

Similar Documents

Publication Publication Date Title
JP2004077476A (en) Apparatus for injecting/mixing liquid droplets
US11383234B2 (en) Electronic control of fluidic species
EP2004316B1 (en) Fluidic droplet coalescence
US6989234B2 (en) Method and apparatus for non-contact electrostatic actuation of droplets
CA2864138C (en) High-speed on demand droplet generation and single cell encapsulation driven by induced cavitation
US6893547B2 (en) Apparatus and method for fluid injection
JP6657379B2 (en) Separation by elastic waves
Yogi et al. On-demand droplet spotter for preparing pico-to femtoliter droplets on surfaces
US6192768B1 (en) Flow-through sampling cell and use thereof
JP2012531302A (en) Fluid injection
JP2015096257A (en) Device for operating packet in micro-channel or other micro-container
CN112076807B (en) Micro-fluidic chip and device for spontaneously forming water-in-oil droplets
JP4252451B2 (en) Liquid droplet forming method and liquid droplet forming apparatus
JP2000329771A (en) Dispenser
JP2008249720A (en) Droplet dispensing system
Li et al. Active femtoliter droplet generation in microfluidics by confined interface vibration
Gast et al. Profile. The development of integrated microfluidic systems at GeSiM
JP4844124B2 (en) Device for supplying micro-droplets of a small amount of sample or reagent
Gu Controlling two-phase flow in microfluidic systems using electrowetting

Legal Events

Date Code Title Description
A300 Application deemed to be withdrawn because no request for examination was validly filed

Free format text: JAPANESE INTERMEDIATE CODE: A300

Effective date: 20061003